Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Decreased level of antibodies and cardiac involvement in patients with chronic Chagas heart disease vaccinated with BCG

Studies indicate that Trypanosoma cruzi is capable of inducing immunological disturbances such as decreased expression of molecules involved in T-cell survival and costimulation for antigen-driven T-cell responses. On the other hand, several reports have described that BCG vaccination induces a T-helper 1-type immune response with protective effects in different pathologies. In this regard, we evaluated whether BCG vaccination coexists with a better clinical and immunological profile of chronic Chagas heart disease (CCHD). We performed a cross-sectional study in T. cruzi seropositive patients categorized according the BCG vaccine background and to the well-established CCHD classification provided by Storino et al. All individuals were subjected to a complete clinical examination. All patients presented detectable levels of autoantibodies anti-p2β, anti-B13, anti-FRA and antiparasite homogenate immunoglobulins, which were unrelated to age and sex distribution or blood pressure values. Comparisons according to BCG vaccination revealed that individuals who had not been vaccinated presented higher values of antibodies, and patients without BCG vaccine had an OR of 6.1 (95 % CI 1.23?29.25, p = 0.02) for globally dilated cardiomyopathy with reduced ejection fraction (Hosmer and Lemeshow test of 5.2 p = 0.73). Our results suggest that BCG vaccination coexists with a better clinical and immunological profile of CCHD, associated with lower cardiac involvement.Fil: Vicco, Miguel Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Bontempi, Iván. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Rodeles, Luz. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Yodice, Agustina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Marcipar, Iván Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin